Summary: Genmab scientists have discovered the basis of instability of human
IgG4 antibodies.
Copenhagen, Denmark; September 13, 2007 - Genmab A/S (OMX: GEN) announced today
its scientists have discovered the basis for the instability of human IgG4
antibodies underlying their biological role in the immune system. In
pre-clinical studies, Genmab discovered that IgG4 antibodies are dynamic and
unstable molecules that naturally exchange their target-binding arms with other
IgG4 molecules. This exchange leads the antibody to essentially become
bispecific with the potential ability to bind to two different targets.
However, the IgG4 antibodies usually do not bind to two different targets
simultaneously in vivo.
This exchange of target-binding arms underlies the anti-inflammatory activity
seen with IgG4 antibodies and may lead to a dampening effect on inflammatory
reactions in certain conditions such as allergies or autoimmune disease. These
dynamic and unstable properties make IgG4 antibodies unpredictable and thus
unfavorable for human therapeutic use, in spite of their potential advantage in
treating diseases for which effector function is not desired.
These findings will be published in the journal Science on September 14. The
studies were performed in collaboration with scientists at Sanquin Research,
Amsterdam and the University of Maastricht, the Netherlands.
“These insights into the mechanisms of human IgG4 antibodies are what led Genmab
to develop the UniBody™ technology platform,” said Prof. Jan G. J. van de
Winkel, Chief Scientific Officer at Genmab. “By removing the hinge region of
the IgG4 antibody molecule, we have created a small, stable and inert
half-molecule with a long half-life called UniBody which may provide effective
treatments for certain types of cancer and autoimmune disease.”
